Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000501296 | SCV000596554 | uncertain significance | not specified | 2017-05-31 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001220273 | SCV001392253 | uncertain significance | Tumor predisposition syndrome 3 | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 361 of the POT1 protein (p.Arg361Cys). This variant is present in population databases (rs372317646, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with POT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 436393). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Sema4, |
RCV002257774 | SCV002527140 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-15 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002257774 | SCV003863629 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-05 | criteria provided, single submitter | clinical testing | The p.R361C variant (also known as c.1081C>T), located in coding exon 9 of the POT1 gene, results from a C to T substitution at nucleotide position 1081. The arginine at codon 361 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV004760540 | SCV005371551 | uncertain significance | not provided | 2024-04-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27149842, 28393830) |